Eckel-Passow Jeanette E, Lachance Daniel H, Decker Paul A, Kollmeyer Thomas M, Kosel Matthew L, Drucker Kristen L, Slager Susan, Wrensch Margaret, Tobin W Oliver, Jenkins Robert B
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Neurooncol Pract. 2022 Mar 12;9(4):259-270. doi: 10.1093/nop/npac017. eCollection 2022 Aug.
Knowledge about inherited and acquired genetics of adult diffuse glioma has expanded significantly over the past decade. Genomewide association studies (GWAS) stratified by histologic subtype identified six germline variants that were associated specifically with glioblastoma (GBM) and 12 that were associated with lower grade glioma. A GWAS performed using the 2016 WHO criteria, stratifying patients by mutation and 1p/19q codeletion (as well as promoter mutation), discovered that many of the known variants are associated with specific WHO glioma subtypes. In addition, the GWAS stratified by molecular group identified two additional novel regions: variants in that were associated with tumors that had an mutation and a variant near that was associated with tumors that had both mutation and 1p/19q codeletion. The results of these germline associations have been used to calculate polygenic risk scores, from which to estimate relative and absolute risk of overall glioma and risk of specific glioma subtypes. We will review the concept of polygenic risk models and their potential clinical utility, as well as discuss the published adult diffuse glioma polygenic risk models. To date, these prior genetic studies have been done on European populations. Using the published glioma polygenic risk model, we show that the genetic associations published to date do not generalize across genetic ancestries, demonstrating that genetic studies need to be done on more diverse populations.
在过去十年中，关于成人弥漫性胶质瘤的遗传和后天遗传学知识有了显著扩展。按组织学亚型分层的全基因组关联研究（GWAS）确定了六个与胶质母细胞瘤（GBM）特异性相关的种系变异和十二个与低级别胶质瘤相关的种系变异。一项使用2016年世界卫生组织标准进行的GWAS，按突变和1p/19q共缺失（以及启动子突变）对患者进行分层，发现许多已知变异与特定的世界卫生组织胶质瘤亚型相关。此外，按分子组分层的GWAS确定了另外两个新区域：与具有某种突变的肿瘤相关的某基因变异，以及与具有该突变和1p/19q共缺失的肿瘤相关的某基因附近的一个变异。这些种系关联的结果已被用于计算多基因风险评分，据此估计总体胶质瘤的相对和绝对风险以及特定胶质瘤亚型的风险。我们将回顾多基因风险模型的概念及其潜在的临床应用，并讨论已发表的成人弥漫性胶质瘤多基因风险模型。迄今为止，这些先前的遗传学研究是在欧洲人群中进行的。使用已发表的胶质瘤多基因风险模型，我们表明，迄今为止公布的遗传关联在不同遗传血统中并不具有普遍性，这表明需要在更多样化的人群中进行遗传学研究。
